Prunin Laurate Derived from Natural Substances Shows Antibacterial Activity against the Periodontal Pathogen Porphyromonas gingivalis.

Periodontal disease is an inflammatory disease caused by infection with periodontopathogenic bacteria. Oral care is essential to prevent and control periodontal disease, which affects oral and systemic health. However, many oral hygiene products currently on the market were developed as disinfectants, and their intense irritation makes their use difficult for young children and older people. This study investigated the antibacterial effects of prunin laurate (Pru-C12) and its analogs on periodontopathogenic bacteria, Porphyromonas gingivalis (P. gingivalis). Pru-C12 and its analogs inhibited in vitro bacterial growth at more than 10 µM and biofilm formation at 50 µM. Among its analogs, only Pru-C12 showed no cytotoxicity at 100 µM. Three of the most potent inhibitors also inhibited the formation of biofilms. Furthermore, Pru-C12 inhibited alveolar bone resorption in a mouse experimental periodontitis model by P. gingivalis infection. These findings may be helpful in the development of oral hygiene products for the prevention and control of periodontal disease and related disorders.

Light Chain Deposition Disease Recurrence in Renal Allograft after Long-Term Remission.

Light chain deposition disease (LCDD) is a rare manifestation of monoclonal gammopathy, which can lead to renal failure. We previously reported a detailed recurrence process in a case of LCDD after renal transplantation. To the best of our knowledge, no report has described the long-term clinical course and renal pathology findings of recurrent LCDD in patients after renal transplantation. In this case report, we describe the long-term clinical presentation and changes in renal pathology of the same patient after early LCDD relapse in a renal allograft. A 54-year-old woman with recurrent immunoglobulin A λ-type LCDD in an allograft was admitted 1 year post-transplant for bortezomib and dexamethasone therapy. At 2 years post-transplantation, a graft biopsy performed after complete remission was achieved, showing some glomeruli with residual nodular lesions similar to the pre-treatment renal biopsy findings. However, the enlarged subendothelial space disappeared. She remained in complete remission serologically for 6 years. Subsequently, the ratio of serum κ/λ-free light chains decreased gradually. She underwent a transplant biopsy approximately 12 years after renal transplantation due to increased proteinuria and decreased renal function. Compared with the previous graft biopsy, almost all glomeruli showed advanced nodule formation and subendothelial expansion. Because the LCDD case relapsed after long-term remission following renal transplantation, protocol biopsy monitoring might be necessary.

Phenolic signals for prehaustorium formation in Striga hermonthica.

Striga hermonthica is a root parasitic plant that causes considerable crop yield losses. To parasitize host plants, parasitic plants develop a specialized organ called the haustorium that functions in host invasion and nutrient absorption. The initiation of a prehaustorium, the primitive haustorium structure before host invasion, requires the perception of host-derived compounds, collectively called haustorium-inducing factors (HIFs). HIFs comprise quinones, phenolics, flavonoids and cytokinins for S. hermonthica; however, the signaling pathways from various HIFs leading to prehaustorium formation remain largely uncharacterized. It has been proposed that quinones serve as direct signaling molecules for prehaustorium induction and phenolic compounds originating from the host cell wall are the oxidative precursors, but the overlap and distinction of their downstream signaling remain unknown. Here we show that quinone and phenolic-triggered prehaustorium induction in S. hermonthica occurs through partially divergent signaling pathways. We found that ASBr, an inhibitor of acetosyringone in virulence gene induction in the soil bacterium Agrobacterium, compromised prehaustorium formation in S. hermonthica. In addition, LGR-991, a competitive inhibitor of cytokinin receptors, inhibited phenolic-triggered but not quinone-triggered prehaustorium formation, demonstrating divergent signaling pathways of phenolics and quinones for prehaustorium formation. Comparisons of genome-wide transcriptional activation in response to either phenolic or quinone-type HIFs revealed markedly distinct gene expression patterns specifically at the early initiation stage. While quinone DMBQ triggered rapid and massive transcriptional changes in genes at early stages, only limited numbers of genes were induced by phenolic syringic acid. The number of genes that are commonly upregulated by DMBQ and syringic acid is gradually increased, and many genes involved in oxidoreduction and cell wall modification are upregulated at the later stages by both HIFs. Our results show kinetic and signaling differences in quinone and phenolic HIFs, providing useful insights for understanding how parasitic plants interpret different host signals for successful parasitism.

Study of Glomerulopathy in Donors after Kidney Transplantation.

INTRODUCTION: Living kidney donation improves the lives of individuals with kidney failure; however, recent studies have suggested that living kidney donors may be at a relatively higher risk of reduced renal function than healthy non-donors. We therefore aimed to evaluate the clinical and pathological findings in living kidney donors who developed kidney disease. METHODS: From January 1991 to May 2019, 1,625 live kidney donations were performed at our hospital. Among the donors, 7 developed kidney disease after donation and underwent open renal biopsy. We studied the clinical and pathological findings of these patients from their clinical records. RESULTS: There were 3 patients with immunoglobulin A (IgA) nephropathy, 2 with membranous nephropathy, 1 with anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis, and 1 with secondary focal segmental glomerulosclerosis (FSGS). All patients with IgA nephropathy had latent IgA deposition on their baseline biopsy. One patient with membranous nephropathy demonstrated findings of membranous nephropathy on the baseline biopsy, despite being asymptomatic. All patients, except for those with ANCA-associated nephropathy and secondary FSGS, recovered from the nephritis or maintained an adequate renal function after treatment. DISCUSSION/CONCLUSION: Baseline biopsy is necessary for assessing the renal condition of kidney donors, and these donors require long-term follow-up based on their baseline biopsy findings. If donors develop kidney disease, appropriate diagnosis and treatment are essential.

Successful treatment of peritoneal dialysis-related peritonitis caused by Dermacoccus nishinomiyaensis.

A 53-year-old man receiving peritoneal dialysis (PD) for 4 months presented with PD-related peritonitis (abdominal pain, turbid peritoneal dialysate effluent, white blood cell in peritoneal dialysate effluent 5350/µL, C-reactive protein 25.56 mg/dL) caused by Dermacoccus (D.) nishinomiyaensis. He was first treated empirically with cefazolin and ceftazidime. After detection of D. nishinomiyaensis in the peritoneal effluent culture collected on the first day of hospitalization, the antibiotics were changed to amoxicillin and vancomycin. After confirming negative-conversion of peritoneal effluent culture, treatment was continued for more than 6 weeks. The peritonitis resolved; he continues peritoneal dialysis without withdrawal from PD or catheter removal. D. nishinomiyaensis is part of resident microbiota of the skin, and its pathogenicity is rarely reported. To date, there is no report of PD-related peritonitis caused by D. nishinomiyaensis. Because it is a slow grower, it may be missed and the peritonitis categorized as culture-negative. Long-term culture is important to detect it. It is difficult to determine the antibiotics that can be used because susceptibility to antibiotics is unknown due to the organism's rarity. Furthermore, the appropriate treatment period is also unknown. Long-term treatment may be useful in PD-related peritonitis caused by D. nishinomiyaensis because it is a slow grower.

Efficacy of Long-Term Treatment With Tolvaptan to Prolong the Time Until Dialysis Initiation in Patients With Chronic Kidney Disease and Heart Failure.

The short-term effectiveness of tolvaptan (TLV) against heart failure has been established. TLV is known to decrease the worsening of renal function more than loop diuretics. Long-term TLV administration decreases the rate of re-hospitalization in heart failure and prevents deterioration of kidney function. If repeated hospitalization for heart failure can be prevented in patients having concurrent chronic kidney disease (CKD), the period until dialysis initiation may be prolonged. We investigated whether long-term TLV management can extend the period until dialysis initiation in patients with CKD and heart failure. A retrospective, observational study was conducted among patients with CKD stage G4 and G5 admitted because of heart failure between April 2013 and July 2018. They were divided into those with TLV and those without TLV. They were followed up until August 2018 and relevant data was collected. Data from 115 patients (68 men and 47 women), with a mean age of 73.4 ± 11.9 (median 76.0 and IQR 66.5-82.0) years and a mean eGFR of 11.8 ± 5.7 (median 9.9 and IQR 7.5-14.8) mL/min/1.73m2 were included in the analysis. Twenty-five patients had received long-term TLV treatment, and 90 had not. Multivariate analysis after adjustment showed that long-term use of TLV significantly lowered the hazard ratio (HR) for time taken to reach dialysis initiation (HR: 0.3286, 95%CI: 0.1282-0.8423, P = 0.0205). Propensity score-matched analysis showed similar results (HR: 0.3220, 95%CI: 0.1107-0.9369, P = 0.0376). In patients with CKD G4 and G5 and heart failure, long-term treatment with TLV can prolong the time until dialysis initiation.

Effect of Oral Alfacalcidol on Clinical Outcomes in Patients Without Secondary Hyperparathyroidism Receiving Maintenance Hemodialysis: The J-DAVID Randomized Clinical Trial.

Importance: Patients with chronic kidney disease have impaired vitamin D activation and elevated cardiovascular risk. Observational studies in patients treated with hemodialysis showed that the use of active vitamin D sterols was associated with lower risk of all-cause mortality, regardless of parathyroid hormone levels. Objective: To determine whether vitamin D receptor activators reduce cardiovascular events and mortality in patients without secondary hyperparathyroidism undergoing hemodialysis. Design, Setting, and Participants: Randomized, open-label, blinded end point multicenter study of 1289 patients in 207 dialysis centers in Japan. The study included 976 patients receiving maintenance hemodialysis with serum intact parathyroid hormone levels less than or equal to 180 pg/mL. The first and last participants were enrolled on August 18, 2008, and January 26, 2011, respectively. The final date of follow-up was April 4, 2015. Interventions: Treatment with 0.5 µg of oral alfacalcidol per day (intervention group; n = 495) vs treatment without vitamin D receptor activators (control group; n = 481). Main Outcomes and Measures: The primary outcome was a composite measure of fatal and nonfatal cardiovascular events, including myocardial infarctions, hospitalizations for congestive heart failure, stroke, aortic dissection/rupture, amputation of lower limb due to ischemia, and cardiac sudden death; coronary revascularization; and leg artery revascularization during 48 months of follow-up. The secondary outcome was all-cause death. Results: Among 976 patients who were randomized from 108 dialysis centers, 964 patients were included in the intention-to-treat analysis (median age, 65 years; 386 women [40.0%]), and 944 (97.9%) completed the trial. During follow-up (median, 4.0 years), the primary composite outcome of cardiovascular events occurred in 103 of 488 patients (21.1%) in the intervention group and 85 of 476 patients (17.9%) in the control group (absolute difference, 3.25% [95% CI, -1.75% to 8.24%]; hazard ratio, 1.25 [95% CI, 0.94-1.67]; P = .13). There was no significant difference in the secondary outcome of all-cause mortality between the groups (18.2% vs 16.8%, respectively; hazard ratio, 1.12 [95% CI, 0.83-1.52]; P = .46). Of the 488 participants in the intervention group, 199 (40.8%) experienced serious adverse events that were classified as cardiovascular, 64 (13.1%) experienced adverse events classified as infection, and 22 (4.5%) experienced malignancy-related serious adverse events. Of 476 participants in the control group, 191 (40.1%) experienced cardiovascular-related serious adverse events, 63 (13.2%) experienced infection-related serious adverse events, and 21 (4.4%) experienced malignancy-related adverse events. Conclusions and Relevance: Among patients without secondary hyperparathyroidism undergoing maintenance hemodialysis, oral alfacalcidol compared with usual care did not reduce the risk of a composite measure of select cardiovascular events. These findings do not support the use of vitamin D receptor activators for patients such as these. Trial Registration: UMIN-CTR Identifier: UMIN000001194.

Exit Site Infection due to Mycobacterium chelonae in an Elderly Patient on Peritoneal Dialysis.

Nontuberculous mycobacteria (NTM) are rarely isolated from peritoneal dialysis (PD)-associated catheter infections. However, NTM infection is usually difficult to treat and leads to catheter loss. Prompt diagnosis is essential for appropriate treatment. A 70-year-old Japanese man who had been on PD for 2 years and with a medical history of 2 episodes of exit site infections (ESIs) due to methicillin-resistant Staphylococcus aureus was admitted to the hospital due to suspected ESI recurrence. However, Gram staining of the pus revealed no gram-positive cocci. Instead, weakly stained gram-positive rods were observed after 7 days of incubation, which were also positive for acid-fast staining. Rapidly growing NTM Mycobacterium chelonae was isolated on day 14. Despite administering a combination antibiotic therapy, ESI could not be controlled, and catheter removal surgery was performed on day 21. Although PD was discontinued temporarily, the patient did not require hemodialysis, without any uremic symptoms. The catheter was reinserted on day 48, and PD was reinitiated on day 61. The patient was discharged on day 65. Antibiotic therapy was continued for 3 months after discharge, with no indications of recurrent infections observed. It is important to consider the risk of NTM infections in patients on PD. Acid-fast staining could be a key test for prompt diagnosis and provision of an appropriate treatment.

Severe refractory TAFRO syndrome requiring continuous renal replacement therapy complicated with Trichosporon asahii infection in the lungs and myocardial infarction: an autopsy case report and literature review.

BACKGROUND: TAFRO (thrombocytopenia, anasarca, fever, reticulin myelofibrosis/renal failure, and organomegaly) syndrome is a systemic inflammatory disorder and unique clinicopathological variant of idiopathic multicentric Castleman disease that was proposed in Japan. Prompt diagnosis is critical because TAFRO syndrome is a progressive and life threating disease. Some cases are refractory to immunosuppressive treatments. Renal impairment is frequently observed in patients with TAFRO syndrome, and some severe cases require hemodialysis. Histological evaluation is important to understand the pathophysiology of TAFRO syndrome. However, systemic histopathological evaluation through autopsy in TAFRO syndrome has been rarely reported previously. CASE PRESENTATION: A 46-year-old Japanese man with chief complaints of fever and abdominal distension was diagnosed with TAFRO syndrome through imaging studies, laboratory findings, and pathological findings on cervical lymph node and bone marrow biopsies. Interleukin (IL)-6 and vascular endothelial growth factor (VEGF) levels were remarkably elevated in both blood and ascites. Methylprednisolone (mPSL) pulse therapy was initiated on day 10, followed by combination therapy with PSL and cyclosporine A. However, the amount of ascites did not respond to the treatment. The patient became anuric, and continuous renal replacement therapy was initiated from day 50. However, the patient suddenly experienced cardiac arrest associated with myocardial infarction (MI) on the same day. Although the emergent percutaneous coronary intervention was successfully performed, the patient died on day 52, despite intensive care. Autopsy was performed to ascertain the cause of MI and to identify the histopathological characteristics of TAFRO syndrome. CONCLUSIONS: Bacterial peritonitis, systemic cytomegalovirus infection, and Trichosporon asahii infection in the lungs were observed on autopsy. In addition, sepsis-related myocardial calcification was suspected. Management of infectious diseases is critical to reduce mortality in patients with TAFRO syndrome. Although the exact cause of MI could not be identified on autopsy, we considered embolization by fungal hyphae as a possible cause. Endothelial injury possibly caused by excessive secretion of IL-6 and VEGF contributed to renal impairment. Fibrotic changes in anterior mediastinal fat tissue could be a characteristic pathological finding in patients with TAFRO syndrome.

Successful Recovery from Spontaneous Spinal Epidural Hematoma in a Patient Undergoing Hemodialysis.

BACKGROUND Spontaneous spinal epidural hematoma (SSEH) occurs in the spinal epidural space in the absence of traumatic or iatrogenic causes, and is considered to be a neurological emergency, as spinal cord compression may lead to neurological deficit. Prompt diagnosis of SSEH can be difficult due to the variety of presenting symptoms, which may resemble those of stroke. Patients who undergo hemodialysis (HD) are at risk of bleeding due to anticoagulation during dialysis and uremia. However, SSEH in HD patients undergoing HD has rarely been reported. CASE REPORT A 70-year-old Japanese man, who has been undergoing maintenance HD for the previous three years, was admitted to Kariya Toyota General Hospital, Aichi, Japan, with acute chest and abdominal pain, and with complete paraplegia. The patient denied any recent trauma or medical procedures. Magnetic resonance imaging showed an extensive hematoma in the thoracic and lumbar epidural space, extending from T8 to L5. The patient's symptoms improved within three hours following hospital admission, and after three days without HD treatment, the SSEH decreased in size, and the patient successfully recovered without residual neurological deficits and without requiring surgery. CONCLUSIONS The management of SSEH in patients undergoing HD can be difficult, due to anticoagulation during dialysis and uremia. Prompt diagnosis and close neurological monitoring are important for appropriate management. In patients whose symptoms improve within a short period, conservative management may be considered.

Acute kidney injury caused by decompression illness successfully treated with hyperbaric oxygen therapy and temporary dialysis.

A 52-year-old Japanese male professional diver was referred to our hospital for decompression illness (DCI). After 1 h of diving operation at 20 m below sea level, he complained of dyspnea, chest pain, and abdominal pain. He dove again, intending to ease the symptoms, but the symptoms were never relieved. He dove for a total of 4 h. No neurological abnormalities were observed. Computed tomography images revealed portal venous gas and mesenteric venous gas, in addition to bubbles in the femoral veins, pelvis, lumbar canal, intracranial sinuses, and joints. Hyperbaric oxygen therapy (HBOT) was immediately administered. His symptoms improved after the first course of HBOT, however, the patient had anuria for almost 36 h after admission and exhibited acute kidney injury (AKI). Serum creatinine and creatine kinase (CK) levels were increased to maximal values of 6.16 mg/dL and 18,963 U/L, respectively. Blood flow signals were not detected on kidney Doppler ultrasound. We considered that AKI was caused by blood flow impairment and capillary leak syndrome due to DCI in addition to rhabdomyolysis secondary to arterial gas embolism in the skeletal muscles. Temporary dialysis was required to correct the acidemia and electrolyte disturbance. Diuretic phase was initiated, and the patient was put off dialysis on day 3. Serum creatinine and CK levels returned to normal on day 11. He was successfully treated without any complications. Although AKI is a rare manifestation, we should consider AKI risk in patients with severe DCI.

Peritoneal dialysis-associated catheter infection caused by Mycobacterium abscessus in an elderly patient who was successfully treated with catheter removal.

An 89-year-old Japanese man on peritoneal dialysis (PD) was suspected of having a PD-associated catheter infection. He visited the hospital because of the discharge of pus from the exit site of his catheter. Gram staining of the pus showed Gram-positive bacilli, but these were acid-fast bacilli. The rapidly growing nontuberculous mycobacteria, Mycobacterium abscessus, was isolated. PD catheter removal and debridement were immediately performed. The patient received combination antibiotic therapy. His clinical course was good, but he required hemodialysis due to the discontinuation of PD. However, the patient and his family chose not to continue hemodialysis even when the symptoms of uremia appeared. Best supportive care was arranged by his primary care physician. M. abscessus is a rare causative organism for PD-associated catheter infections and is difficult to treat. In our case, a rapid and precise diagnosis was made using acid-fast staining and Mycobacterium culture. The risk of nontuberculous mycobacterial infections should be considered in patients on PD.

Ethical dilemmas facing chief nurses in Japan: A Pilot study.

BACKGROUND: Chief nurses are most likely to take the lead in discussing and working to resolve ethical dilemmas, creating an ethical culture within their organization that results in effective ethics training. As the first step in this process, there is a need to define the kinds of ethical dilemmas that chief nurses grapple with on a regular basis as a target for future study. RESEARCH DESIGN: Anonymous written questionnaires and semi-structured interviews. ETHICAL CONSIDERATIONS: All research procedures were approved by the Chubu University Ethics Review Board, the research institution to which the authors belong (authorization no. 250016). FINDINGS AND DISCUSSION: Responses from four chief nurses indicated that ethical dilemmas could be categorized as either those related to patient dignity or those related to management (unique to their roles as administrators). It was also learned that chief nurses struggle with the fact that although they consult with their superiors and others, these efforts do not lead to resolution. The expectation is that going forward, chief nurses will play a central role in acting as coordinators with physicians to promote better communication as well as lead group discussions aimed at providing care that respects patient dignity.

[Comparison of benefits to non-dialysis CKD patients between darbepoetin alpha and epoetin beta pegol].

BACKGROUND: Erythropoiesis-stimulating agents (ESAs) are the mainstay of treatment for renal anemia in chronic kidney disease (CKD) patients. However, the difference in hematopoietic effect between darbepoetin alfa (DA) and continuous erythropoiesis receptor activator (CERA) has remained unclear in non-dialysis CKD patients. Another purpose of this study was to analyze the red blood cells indices under treatment with these two ESAs in ESA-naïve CKD patients. METHODS: This study was designed as a multicenter retrospective observational investigation, and included 61 patients receiving DA (group DA) and 36 patients receiving CERA (group CERA) for at least six months. Relative effect of these ESAs was determined by comparing means of the individual monthly average of the area under the curve above the initial level of hemoglobin (Hb), hematocrit (Hct), and red blood cell count (RBC) with the trapezoidal rule, which are maintenance ratios. Serial changes in mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) were also evaluated. RESULTS: No differences were found in the mean ratios of Hb, Hct, and RBC, and maintenance ratios of these parameters. The ratio of MCH in group CERA was decreased compared with that in group DA. Subsequent decrease in MCV was also remarkable in group CERA. CONCLUSIONS: It is speculated that iron demand increased during the administration of CERA, which was suggested by changes in the red cell indices. Reticulocyte indices and iron-related parameters could provide a more detailed explanation and the significance of iron supplementation during administration of CERA should be clarified when compared with other types of ESA.

Management of Diabetes Associated with Nephrotic Syndrome: Therapeutic Potential of Dapagliflozin for Protracted Volume Retention.

A 48-year-old female was admitted to our hospital presenting with a chief complaint of progressive swelling because of diabetic nephrotic syndrome. Dapagliflozin seemed to play a role in accelerating the patient's urinary sodium excretion as well as reducing gross fluid retention despite the fact that her nephrotic condition was resistant to furosemide. Our experience emphasizes a potential novel approach to overcoming loop diuretic resistance using this agent among some subsets of type 2 diabetic subjects complicated with severe volume accumulation. We believe that combination treatment consisting of dapagliflozin and furosemide may produce diuretic synergy via sequential nephron blockade. The accumulation of more experience with additional cases similar to ours requires continuous and careful attention.

Coronary microvascular function is independently associated with left ventricular filling pressure in patients with type 2 diabetes mellitus.

BACKGROUND: Left ventricular (LV) diastolic dysfunction is known as an early marker of myocardial alterations in patients with diabetes. Because microvascular disease has been regarded as an important cause of heart failure or diastolic dysfunction in diabetic patients, we tested the hypothesis that coronary flow reserve (CFR), which reflects coronary microvascular function, is associated with LV diastolic dysfunction in patients with type 2 diabetes. METHODS: We studied asymptomatic patients with type 2 diabetes but without overt heart failure. Transthoracic Doppler echocardiography was performed that included pulsed tissue Doppler of the mitral annulus and CFR of the left anterior descending artery (induced by adenosine 0.14 mg/kg/min). The ratio of mitral velocity to early diastolic velocity of the mitral annulus (E/e') was used as a surrogate marker of diastolic function. We also evaluated renal function, lipid profile, parameters of glycemic control and other clinical characteristics to determine their association with E/e'. Patients with LV ejection fraction <50%, atrial fibrillation, valvular disease, regional wall motion abnormality, renal failure (serum creatinine >2.0 mg/dl) or type 1 diabetes were excluded. Patients with a CFR <2.0 were also excluded based on the suspicion of significant coronary artery stenosis. RESULTS: We included 67 asymptomatic patients with type 2 diabetes and 14 non-diabetic controls in the final study population. In univariate analysis, age, presence of hypertension, LV mass index, estimated glomerular filtration rate and CFR were significantly associated with E/e'. Multivariate analysis indicated that both LV mass index and CFR were independently associated with E/e'. In contrast, there were no significant associations between parameters of glycemic control and E/e'. CONCLUSIONS: CFR was associated with LV filling pressure in patients with type 2 diabetes. This result suggests a possible link between coronary microvascular disease and LV diastolic function in these subjects.

Febuxostat for hyperuricemia in patients with advanced chronic kidney disease.

Febuxostat is a nonpurine xanthine oxidase (XO) inhibitor, which recently received marketing approval. However, information regarding the experience with this agent among advanced chronic kidney disease (CKD) patients is limited. In the current study, we investigated the effects of oral febuxostat in patients with advanced CKD with asymptomatic hyperuricemia. We demonstrated, for the first time, that not only the serum levels of uric acid (UA) but also those of 8-hydroxydeoxyguanosine, an oxidative stress marker, were significantly reduced after six months of febuxostat treatment, with no adverse events. These results encouraged us to pursue further investigations regarding the clinical impact of lowering the serum UA levels with febuxostat in advanced CKD patients in terms of concomitantly reducing oxidative stress via the blockade of XO. More detailed studies with a larger number of subjects and assessments of the effects of multiple factors affecting hyperuricemia, such as age, sex, and dietary habits, would shed light on the therapeutic challenges of treating asymptomatic hyperuricemia in patients with various stages of CKD.

Comparison of phenotype and outcome in microscopic polyangiitis between Europe and Japan.

OBJECTIVE: There are differences between Europe and Japan in the incidence and antineutrophil cytoplasmic antibody (ANCA) serotype of patients with microscopic polyangiitis (MPA). However, differences in phenotype or outcome have not been explored. We aimed to identify differences in phenotype and outcome of MPA between Europe and Japan. METHODS: Sequential cohorts of patients with MPA and renal limited vasculitis were collected from European and Japanese centers (n = 147 and n = 312, respectively). Trial databases from the European Vasculitis Society and the Japanese patients with Myeloperoxidase (MPO)-ANCA-Associated Vasculitis (JMAAV) trial were studied (n = 254 and n = 48, respectively). We evaluated baseline characteristics including ANCA status and organ involvement, treatment, survival, and renal survival. Differences in survival and renal survival were studied using multivariate analysis. RESULTS: The non-trial cohorts showed patients with MPA in Japan had a higher age at onset, more frequent MPO-ANCA positivity, lower serum creatinine, and more frequent interstitial pneumonitis than those in Europe (all p < 0.01). Comparisons between the trial databases demonstrated similar results. Cumulative patient survival and renal survival rates were not different between Europe and Japan (p = 0.71 and p = 0.38, respectively). Multivariate analysis identified age at onset, serum creatinine, gastrointestinal, and respiratory involvement as factors with higher risk of death. For endstage renal failure, serum creatinine and use of plasma exchange were identified as factors with higher risk, and immunosuppressant use as lower risk factors. CONCLUSION: Phenotypes in patients with MPA were different between Europe and Japan. However, the outcomes of patient survival and renal survival were similar.